A truncation variant of the cation channel P2RX5 is upregulated during T cell activation

PLoS One. 2014 Sep 2;9(9):e104692. doi: 10.1371/journal.pone.0104692. eCollection 2014.

Abstract

Members of the P2X family of ligand-gated cation channels (P2RX) are expressed by various cell types including neurons, smooth- and cardiac muscle cells, and leukocytes. The channels mediate signalling in response to extracellular ATP. Seven subunit isoforms (P2RX1-P2RX7) have been identified and these can assemble as homo- and heterotrimeric molecules. In humans, P2RX5 exists as a natural deletion mutant lacking amino acids 328-349 of exon 10, which are part of transmembrane (TM) 2 and pre-TM2 regions in other organisms like rat, chicken and zebrafish. We show that P2RX5 gene expression of human T lymphocytes is upregulated during activation. P2RX5 is recruited to the cell surface. P2RX5-siRNA-transfected CD4+ T cells produced twofold more IL-10 than controls. Surface and intracellular P2RX5 expression was upregulated in activated antigen-specific CD4+ T cell clones. These data indicate a functional role of the human P2RX5 splice variant in T cell activation and immunoregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Membrane / metabolism
  • Cell Polarity
  • Clone Cells
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Interleukin-10 / metabolism
  • Lymphocyte Activation / immunology*
  • Lymphocyte Subsets / immunology
  • Mutant Proteins / metabolism*
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Protein Transport
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Purinergic P2X5 / genetics*
  • Receptors, Purinergic P2X5 / metabolism
  • Up-Regulation* / genetics

Substances

  • Mutant Proteins
  • P2RX5 protein, human
  • Protein Subunits
  • RNA, Messenger
  • Receptors, Purinergic P2X5
  • Interleukin-10

Grants and funding

This work was supported in part by the Deutsche Forschungsgemeinschaft, DFG (Ma 965/8-1, Po 137/39-1) and the Hertie-Stiftung (R.M. and O.P.) and the Fonds der Chemischen Industrie. The inims was supported by the Gemeinnützige Hertie Stiftung. The Neuroimmunology and MS Research Section (nims) is supported by the Clinical Research Priority Program MS (CRPPMS) of the University Zurich. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.